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Objectives: Biofilm is thought to be involved in the persistent bacterial infections caused by nontypeable Haemophilus influenzae (NTHi). This study aims to evaluate the efficacy of antibiotics against NTHi biofilms., Methods: A 96-wells pin replicator assay was applied for evaluation of antimicrobial efficacies against NTHi biofilms. The NTHi IH-202 strain for the standard and 10 clinical strains were evaluated, as well as the viability of NTHi in biofilms after antimicrobial exposures., Results: Biofilms formed by IH-202 strain accumulated during incubation. AMPC if not high concentrations, neither reduce or inhibit biofilm formation, nor eradicate matured NTHi biofilms. The NTHi in matured biofilm were alive after exposure to amoxicillin (AMPC). Even high concentration of AMPC produced live NTHi after suspension of exposure, while tosufloxacin and garenoxacin inhibited biofilm formation of NTHi and eradicated matured biofilms. The respiratory quinolones, but not AMPC, killed NTHi in biofilms even at sub-MIC., Conclusions: NTHi persists in biofilms, even after exposure to AMPC. These findings may eventually lead to a better understanding of effective use of antibiotics to eradicate NTHi growing as biofilms, or even to the development of novel therapeutic agents for treating patients with mucosal NTHi biofilm infections. Meanwhile, respiratory quinolones are attractive agents in reducing NTHi biofilm formation and destroying established biofilm., Competing Interests: Declaration of competing interest The authors declare financial support from FUJIFILM Toyama Chemical Co., Ltd. The funder had no role in the experimental design, implementation of the study, interpretation of the data, or decision to submit the manuscript for publication. This does not alter the authors’ adherence to any publication policies on sharing data and materials., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Despite endoscopic thyroid surgery contributing to excellent cosmetic outcomes, it requires longer surgical time than open surgery. This study evaluates the factors associated with operative time in video-assisted neck surgery., Methods: We retrospectively reviewed patients who underwent hemithyroidectomy by video-assisted neck surgery at a single hospital between 2017 and 2021. The clinical parameters were evaluated: age, sex, body weight, body mass index, coexistence of Hashimoto thyroiditis, side of operation, surgical approach to thyroid (midline approach or lateral approach), operation time, amount of blood loss during surgery, maximum tumor diameter and tumor volume, and postoperative complications. These parameters were compared to investigate the association of operative time and surgical approach., Results: Seventy consecutive patients were enrolled in this study, the median age at operation was 50 years, and there were 6 (8.6%) men and 64 (91.4%) women. The median body weight and body mass index at operation were 56.6 kg and 21.5, respectively. Coexistence of Hashimoto thyroiditis was found in 17 (24.3%) patients. Significant differences were found between the groups with longer and shorter operation time than median 201 minutes in surgical approaches to the thyroid ( P  < .001) and the amount of bleeding during surgery ( P  = .039). There were no differences in other candidates between the groups. Median operation times were 242 minutes in midline approach and 131 minutes in lateral approach ( P  < .001)., Conclusion: The lateral approach of video-assisted neck surgery to the thyroid can contribute to shortened surgical time in the case of benign thyroid nodules., (© 2022 The Authors.)

Objectives: In 2016, Japanese Society of Chemotherapy and Japan Society for Surgical Infection presented the practical guideline for appropriate usage of antimicrobial agents to prevent postoperative infections. This study aims to exhibit the validity of the guideline as a series of effective strategies for prevention of surgical site infections (SSIs) during reconstructive surgery of the head and neck cancer., Methods: We retrospectively evaluated patients who underwent head and neck reconstructive surgery with free or pedicle flaps in a single institute in Japan between July 2010 and July 2020. We evaluated the incidence of SSIs, patient backgrounds, and microbiological characteristics on the basis of antimicrobial prophylaxis recommended by the guideline., Results: Enrolled in this study were 102 patients in our institution who underwent head and neck reconstructive surgery with free or pedicle flaps between July 2010 and July 2020. In the period between January 2018 to July 2020 after the SSI guideline was advocated (SSI guideline period), the ratio of administration of sulbactam/ampicillin (SBT/ABPC) was significantly higher (P < 0.001) and the duration of prophylactic antimicrobial treatment was significantly shorter than in the period between July 2010 to December 2017 before the SSI guideline was advocated (Pre-SSI guideline period) (P < 0.001). Incidence of SSIs were similar, even when antibiotic use was changed to be short-term single-agent administration in accordance with the practical guideline., Conclusions: Adherence to the current Japanese practical guideline on appropriate antimicrobial prophylaxis for SSIs can shorten the duration of usage of antimicrobial treatment without increasing the risk for occurrence of SSIs., (Copyright © 2021. Published by Elsevier Ltd.)

Objectives: We investigated changes in prescriptions for antimicrobial agents to treat children with acute otitis media (AOM)., Methods: A descriptive study using an electronic medical record database. Of 199,896 patients enrolled between 2001 and 2019, a total of 10,797 were aged <16 years and had AOM as their first and primary disease (overall pediatric AOM cohort). In addition, 4786 patients with AOM without other comorbidities (pediatric AOM cohort) were included., Results: In the overall pediatric AOM cohort, the age distribution ranged from 11% to 23% for those younger than 2 years and from 66% to 77% for those younger than 6 years, with no change over time. In the pediatric AOM cohort, the antimicrobial prescription rate was 91% in 2001 but declined to 40% by 2019. Antimicrobial use increased from 0% to 75% for penicillins, whereas use of cephalosporins decreased from 84% to 10%. The prescription rate for acetaminophen alone increased from 33% to 58%. There were no differences in the incidence of adverse reactions among the prescribed antimicrobials., Conclusions: Due to education efforts and promotion of the proper use of antimicrobials through means such as the Clinical practice guidelines for the diagnosis and management of acute otitis media in children (2006) and the Manual of Antimicrobial Stewardship (2016), a change in the use of antimicrobials occurred, leading to a trend to more proper use of these agents., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Despite tremendous success of pneumococcal conjugated vaccine and antimicrobial treatment by amoxicillin, acute otitis media (AOM) still remains as a great medical concern. Failure of antimicrobial treatment includes several factors. The middle ear cavity is surrounded by bone tissue, which makes it difficult to maintain sufficient concentration of antibiotics. Tympanic membrane of AOM patients thickens and actually becomes a barrier for topical therapy. This review discusses novel antimicrobial treatment strategies based on drug delivery systems (DDS) for AOM. To deliver drugs enough to kill the pathogenic bacteria without systemic side effects, the development of new antimicrobial treatment strategy applying innovative drug DDS has been expected. The sustained-release DDS can achieve sufficient time for antimicrobial concentrations to exceed minimum inhibitory concentration (MIC) for time-dependent antibiotics as well as enough maximum concentration for dose-dependent antibiotics to eradicate causative pathogens in the middle ear. The development of trans-tympanic membranes of DDS, such as hydrogels with chemical permeation enhancers (CPEs), is another attractive strategy. Phage is a promising strategy for developing DDS-based therapies. The DDS formulations enable antimicrobial treatment of AOM by a single dose and thus, an attractive future antimicrobial treatment for AOM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kono, Umar, Takeda, Ohtani, Murakami, Sakatani, Kaneko, Nanushaj and Hotomi.)

Recently recognized slow slip events (SSEs) recurring in the deeper extensions of seismogenic zones along plate boundaries are drawing attention to their potential for triggering megathrust earthquakes that rupture the entire seismogenic zone. We describe how earthquakes simulated in a single-degree-of-freedom model are synchronized to the rhythm of imposed periodic SSEs. The time lag t Q from the one most recent SSE to a seismic event varies with system parameters and may take a broad range of eligible values between 0 and T SSE (SSE recurrence period). Earthquakes were found to synchronize with SSEs in various patterns depending on the proportion of SSE-driven loading within an SSE cycle, the recurrence period of the SSEs, and the duration of the SSEs, although synchronization itself remained a prevalent feature. Asynchrony was found only for long SSE durations.

Conclusion: The results of this study indicate that transient receptor potential subfamily 1 (TRPV1) may play a functional role in sensory cell physiology and that TRPV4 may be important for fluid homeostasis in the inner ear., Objective: To analyze the expression of TRPV1 and -4 in the normal guinea pig inner ear., Material and Methods: Albino guinea pigs were used. The location of TRPV1 and -4 in the inner ear, i.e. cochlea, vestibular end organs and endolymphatic sac, was investigated by means of immunohistochemistry., Results: Immunohistochemistry revealed the presence of TRPV1 in the hair cells and supporting cells of the organ of Corti, in spiral ganglion cells, sensory cells of the vestibular end organs and vestibular ganglion cells. TRPV4 was found in the hair cells and supporting cells of the organ of Corti, in marginal cells of the stria vascularis, spiral ganglion cells, sensory cells, transitional cells, dark cells in the vestibular end organs, vestibular ganglion cells and epithelial cells of the endolymphatic sac.

Objective: To perform a trial to assess the efficacy of radical scavengers, i.e. rebamipide, vitamin C and glutathione, for the treatment of Ménière's disease (MD)., Material and Methods: Rebamipide (300 mg/day), vitamin C (600 mg/day) and/or glutathione (300 mg/day) were given orally for at least 8 weeks to 25 patients with poorly controlled MD., Results: Of 22 patients, 21 showed marked improvement of vertigo; 12/27 ears showed improvement of hearing disorders; 17/27 ears showed improvement of tinnitus; and 18/25 patients showed improvement of disability., Conclusion: This study suggests that treatment using radical scavengers has the potential to become an effective new therapy for MD.